› 6ckx

X-ray diffraction
2.8Å resolution

Structure of CDK12/CycK in complex with a small molecule inhibitor N-(4-(1-methyl-1H-pyrazol-4-yl)phenyl)-N-((1r,4r)-4-(quinazolin-2-ylamino)cyclohexyl)acetamide

Released:
DOI: 10.2210/pdb6ckx/pdb
PDB entry 6ckx coloured by chain, front view.
PDB entry 6ckx coloured by chain, side view.
PDB entry 6ckx coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery of 3-Benzyl-1-( trans-4-((5-cyanopyridin-2-yl)amino)cyclohexyl)-1-arylurea Derivatives as Novel and Selective Cyclin-Dependent Kinase 12 (CDK12) Inhibitors.
Ito M, Tanaka T, Toita A, Uchiyama N, Kokubo H, Morishita N, Klein MG, Zou H, Murakami M, Kondo M, Sameshima T, Araki S, Endo S, Kawamoto T, Morin GB, Aparicio SA, Nakanishi A, Maezaki H, Imaeda Y
J Med Chem 61 7710-7728 (2018)
PMID: 30067358

Function and Biology Details

Reactions catalysed: 
ATP + a protein = ADP + a phosphoprotein
ATP + [DNA-directed RNA polymerase] = ADP + [DNA-directed RNA polymerase] phosphate
Biochemical function:
Biological process:
Cellular component:
  • not assigned
Sequence domains:

Structure analysis Details

Assembly composition:
hetero dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-131171 (preferred)
Entry contents:
2 distinct polypeptide molecules
Macromolecules (2 distinct):
Cyclin-dependent kinase 12 Chains: A, C
Molecule details ›
Chains: A, C
Length: 351 amino acids
Theoretical weight: 40.76 KDa
Source organism: Homo sapiens
Expression system: unidentified baculovirus
UniProt:
  • Canonical: Q9NYV4 (Residues: 714-1063; Coverage: 24%)
Gene names: CDK12, CRK7, CRKRS, KIAA0904
Sequence domains: Protein kinase domain
Structure domains:
Cyclin-K Chains: B, D
Molecule details ›
Chains: B, D
Length: 268 amino acids
Theoretical weight: 31.43 KDa
Source organism: Homo sapiens
Expression system: unidentified baculovirus
UniProt:
  • Canonical: O75909 (Residues: 1-267; Coverage: 46%)
Gene names: CCNK, CPR4
Sequence domains:
Structure domains: Cyclin-like

Ligands and Environments

2 bound ligands:
Ligand MG 3 x MG
Ligand 8M1 2 x 8M1
1 modified residue:
Ligand TPO 2 x TPO

Experiments and Validation Details

Entry percentile scores
X-ray source: ALS BEAMLINE 5.0.3
Spacegroup: P212121
Unit cell:
a: 96.596Å b: 107.53Å c: 138.324Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.21 0.208 0.251
Expression system: unidentified baculovirus

Quick links

Citations

6 review citations

Synthetic Lethality through the Lens of Medicinal Chemistry.
Myers et al. (2020)
5 more

2 mentions without citation

Discovery and resistance mechanism of a selective CDK12 degrader.
Jiang et al. (2021)
1 more